期刊
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
卷 121, 期 -, 页码 260-268出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejps.2018.06.004
关键词
Melt electrospinning; Melt-spun fibers; Poorly water-soluble drug; Indomethacin; Soluplus (R); Drug-polymer interactions
资金
- Estonian national research projects [PUT1088, IUT-34-18]
- Estonian Research Council
- Ministry of Education and Research
The present study introduces a modified melt-electrospinning (MES) method for fabricating the melt-electrospun fibers (MSFs) of a poorly water-soluble drug and carrier polymer. The MES of poorly water-soluble model drug indomethacin (IND) and hydrophilic carrier polymer, Soluplus (R) (SOL) were prepared at a 1:3 drug-polymer weight ratio. Water was used as an external plasticizer to regulate a MES processing temperature and to improve fiber formation. The fiber size, surface morphology, physical solid state, drug-polymer (carrier) interactions, thermal and chemical stability and dissolution behavior of MSFs were investigated. Solid state nuclear magnetic resonance spectroscopy (NMR) was used to measure T1(H-1), and the domain size of IND in MSFs (25-100 nm) was calculated from these results. Solid-state and thermal analysis confirmed the presence of amorphous solid dispersions of IND and SOL. IND was found to be chemically stable during an entire MES process. Only small drug content variability of different MSF batches was detected with high performace liquid chromatography (HPLC). Given findings were verified with the liquid NMR spectroscopy. The dissolution of MSFs was significantly faster than that of physical mixtures (PMs) or pure drug. The enhanced dissolution of MSFs was caused by high surface area, amorphous state of the drug and solubilizing properties of the carrier polymer (SOL).
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